Synthesis and evaluation of antioxidant properties of 2-substituted quinazolin-4(3H)-ones

Mravljak, Janez (author), Slavec, Lara (author), Hrast, Martina (author), Sova, Matej (author)

Quinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3H)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TEAC$_{CUPRAC}$, to obtain key information about the structure–antioxidant activity relationships of a diverse set of substituents at position 2 of the main quinazolinone scaffold. Regarding the antioxidant activity, ABTS and TEAC$_{CUPRAC}$ assays were more sensitive and gave more reliable results than the DPPH assay. To obtain antioxidant activity of 2-phenylquinazolin-4(3H)-one, the presence of at least one hydroxyl group in addition to the methoxy substituent or the second hydroxyl on the phenyl ring in the ortho or para positions is required. An additional ethylene linker between quinazolinone ring and phenolic substituent, present in the second series (compounds 25a and 25b), leads to increased antioxidant activity. Furthermore, in addition to antioxidant activity, the derivatives with two hydroxyl groups in the ortho position on the phenyl ring exhibited metal-chelating properties. Our study represents a successful use of three different antioxidant activity evaluation methods to define 2-(2,3-dihydroxyphenyl)quinazolin-4(3H)-one 21e as a potent antioxidant with promising metal-chelating properties.

• Language: English
• Keywords: quinazolinone, synthesis, antioxidant, DPPH, ABTS, CUPRAC, metal-chelating properties
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 16 str.
• Numbering: Vol. 26, iss. 21, art. 6585
• PID: 20.500.12556/RUL-136429
• UDC: 543:615.4:54
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules26216585
• COBISS.SI-ID: 83008003
• Publication date in RUL: 04.05.2022

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.11.2021

Secondary language

• Language: Slovenian
• Keywords: antioksidanti, sinteze, lastnosti keliranja kovin, kinazolinoni, farmacevtska kemija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: ARRS - Slovenian Research Agency
• Project number: J1-1709
• Name: Strukturni vpogled v mehanizem tvorbe površine bakterije Clostridium difficile